We have suggested that age-related alterations in the metabolism of chemical carcinogens may be one factor responsible for the increased incidence of cancer with advancing age. In support of this hypothesis, previous work from our laboratory has shown that senescence in rodents is accompanied by changes in the activity of those hepatic enzymes which are responsible for the activation and further metabolism of polycyclic aromatic hydrocarbons (PAH). These changes, in turn, result in an enhancement of mutagenicity of the metabolites of 3,4-benzo(a)pyrene and 2-fluorenamine in a bacterial test system, and an enhanced covalent binding of radioactively-labelled carcinogens to calf thymus DNA in an in vitro test system. In order to better understand these observations, we propose to examine the functional linkage between AHH and EH in the liver of rodents of different ages. These studies will be carried out by inhibiting hepatic EH activity with 1,1,1,-trichloropropeneoxide in rodents of different ages, and examining the metabolites of PAH both prior to, and following, inhibition of EH activity. In addition, we propose to extend our effort to include the metabolism of PAH in the lung of rodents of varying age, since this organ is a major target for carcinogenesis by this class of compounds.